Analysis of the effect of traditional health methods on improving respiratory function using bioimaging

• Project/Area Number: 19K11789
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: Fujita Eri 東京農工大学, 工学(系)研究科(研究院), 研究員 (50466877)
• Co-Investigator(Kenkyū-buntansha): 清水 美穂 東京農工大学, 工学(系)研究科(研究院), 客員准教授 (00500399) ; 平工 志穂 東京女子大学, 現代教養学部, 教授 (30302821) ; 田中 幸夫 東京農工大学, 工学(系)研究科(研究院), 名誉教授 (60179794) ; 跡見 順子 東京農工大学, 工学(系)研究科(研究院), 客員教授 (90125972)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 卵殻膜 / 細胞外マトリクス / 肺線維症 / 線維症 / 呼吸機能 / 肺線維化 / バイオイメージング

Outline of Research at the Start

高齢化に伴い呼吸器疾患は増加しており、特に肺線維症については根本的な治療法がない。肺線維症の緩和を目指し、入手が容易で伝統的に創傷治癒効果があるとされてきたニワトリ卵殻膜に注目した。卵殻膜は、組織弾力性に寄与するⅢ型コラーゲンなどの細胞外マトリクスを誘導することや、卵殻膜の長期摂取が呼吸機能を改善することを明らかにしてきた。卵殻膜が細胞外マトリクスの恒常性を改善する機能を利用した、呼吸機能改善を目指す。さらに二光子励起顕微鏡を利用したバイオイメージングにより、生体への卵殻膜摂取効果をダイナミックに分析し、運動療法や呼吸法と組み合わせることで高齢社会における新規の健康戦略を開発する。

Outline of Final Research Achievements

In a human study, respiratory function was significantly increased in the group that ingested eggshell membrane compared to the control group. Radiolabeled eggshell membrane was also orally administered to mice to clarify the pharmacokinetics of eggshell membrane. Image analysis and gene expression analysis of mouse lung tissue and lung fibroblasts revealed that eggshell membrane significantly increased the expression level and secretion of decorin, which is known to prevent fibrosis and maintain healthy collagen fiber formation. Oral administration of eggshell membrane to mice models of pulmonary fibrosis significantly increased the level of decorin in the alveoli and reduced TAZ nuclear migration, a marker of pulmonary fibrosis. These results suggest that eggshell membrane improves the extracellular environment of lung tissue, thereby reducing pulmonary fibrosis and improving respiratory function.

Academic Significance and Societal Importance of the Research Achievements

高齢化に伴い呼吸器疾患は増加しており、特に肺線維症については根本的な治療法がない。肺線維症の緩和を目指し、入手が容易で伝統的に創傷治癒効果があるとされてきたニワトリ卵殻膜に注目した。我々は天然素材・卵殻膜が、弾力性に富む細胞外マトリクス成分であるデコリンやIII型コラーゲンの発現を誘導するという作用機序を利用し、呼吸機能改善や肺線維症にも有効なアプローチを開発した。卵殻膜の経口摂取は、肺組織の細胞外環境を改善することにより肺の健康に寄与する栄養/機能性食品として期待できる。

Research Products

• [Journal Article] Application of Neutron-Irradiated ⁶Li (n, α) ³H Reaction to a Protein-Based Fibrous Non-Woven Fabric Biopolymer: Radiolabeling of Cross-Linked Natural Fibrous Chicken Eggshell Membranes and Their Whole-Body Tissue Distribution after Oral Ingestion in Mice (2021)
  • Author(s): Ohto-Fujita Eri、Nogawa Norio、Shimizu Miho、Ijiri Ken-ichi、Hasebe Yukio、Atomi Yoriko
  • Journal Title: Journal of Fiber Science and Technology Volume: 77 Issue: 6 Pages: 182-187
  • DOI: 10.2115/fiberst.2021-0018
  • NAID: 130008052794
  • ISSN: 2189-7654
  • Year and Date: 2021-06-15
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Eggshell Membrane Powder Intake on the Body Function of Healthy Individuals (2021)
  • Author(s): Ohto-Fujita Eri、Hatakeyama Nozomi、Atomi Aya、Yasuda Shunsuke、Kodama Shoki、Atomi Tomoaki、Tanaka Kazuya、Noboru Hirose、Harada Kenji、Asano Yoshihide、Watanabe Toshiyuki、Hasebe Yukio、Shimizu Miho、Atomi Yoriko
  • Journal Title: Journal of Fiber Science and Technology Volume: 77 Issue: 10 Pages: 258-265
  • DOI: 10.2115/fiberst.2021-0029
  • NAID: 130008107353
  • ISSN: 2189-7654
  • Peer Reviewed / Open Access
• [Journal Article] Application of neutron-irradiated 6Li (n, α) 3H reaction to a protein-based fibrous non‐woven fabric biopolymer: Radiolabeling of cross-linked natural fibrous chicken eggshell membranes and their whole-body tissue distribution after oral ingestion in mice (2021)
  • Author(s): Eri Ohto-Fujita, Norio Nogawa, Miho Shimizu, Ken-ichi Ijiri, Yukio Hasebe, Yoriko Atomi
  • Journal Title: Journal of Fiber Science and Technology Volume: -
  • NAID: 130008052794
  • Peer Reviewed / Open Access
• [Presentation] リコイルタグ法によるニワトリ胚細胞外マトリックス卵殻膜のトリチウム標識とマウス経口摂取後の全身組織分布 (2021)
  • Author(s): 跡見順子, 大戸-藤田恵理、野川憲夫、清水美穂、井尻憲一、長谷部由紀夫
  • Organizer: 2021日本結合組織学会学術大会
• [Presentation] Radiolabeling of cross-linked natural fibrous chicken eggshell membranes and their whole-body tissue distribution after oral ingestion in mice (2021)
  • Author(s): Yoriko Atomi, Eri Ohto-Fujita, Norio Nogawa, Miho Shimizu, Ken-ichi Ijiri, Yukio Hasebe
  • Organizer: CELL BIO virtual 2021
  • Int'l Joint Research
• [Presentation] Verification of the antifibrotic effect of chicken eggshell membrane ingestion using a bleomycin pulmonary fibrosis mouse model (2020)
  • Author(s): Yoriko Atomi, Eri Ohto-Fujita, Natsumi Shibayama, Ryota Hosoda, Miho Shimizu, Aya Atomi, Shinya Horinouchi, Shinya Miyazaki, Tomoaki Murakami, Yoshihide Asano, Yukio Hasebe
  • Organizer: 2020日本結合組織学会学術大会
• [Presentation] Oral eggshell membrane administration attenuated lung fibrosis via type III collagen- and decorin-mediated wound healing (2020)
  • Author(s): Y Atomi, E Ohto-Fujita, M Shimizu, A Atomi, N Hatakeyama, N Shibayama, R Hosoda, S Horinouchi, T Murakami, S Miyazaki, M Kurimoto, S Yasuda, S Kodama, N Nogawa, T Atomi, K Tanaka, N Hirose, K Harada, Y Asano, T Watanabe, Y Hasebe
  • Organizer: 2020ASCB (CELL BIO virtual 2020, An online ASCB)
  • Int'l Joint Research